Non-nucleoside linkers for convenient attachment of labels to oligonucleotides using standard synthetic methods

Abstract

Pseudonucleosides and pseudonucleotides are useful in the synthesis of oligomers which contain these components as a means to derivatize the resulting oligonucleotide to useful substituents such as chelators, intercalators, or lipophilic compounds. In general, these pseudonucleotide components are of the formula: ##STR1## wherein each Y is independently O or S; each X is independently H, PO 3 -2 , an activated nucleotide synthesis coupling moiety, a protecting group, a nucleoside, a nucleotide or a nucleotide sequence, or comprises a solid support; F is a functional group capable of linking an additional moiety or said group already reacted to effect the binding of said additional moiety; □ is an organic backbone which does not contain additional F or Y-X substituents and which is either achiral even when the Y-X substituents are different, or is a single enantiomer of a chiral compound; with the proviso that at least one X is a nucleoside, nucleotide, nucleotide sequence, an activated nucleotide synthesis coupling moiety, or comprises a solid support, or F represents said functional group already reacted with an additional group. Oligonucleotides having the pseudonucleoside at the 3' terminus are particularly stable in vivo.

We claim: 
     
       1. A compound of the formula ##STR7## wherein n is an integer of 1 to 10; each Y is independently O or S; and wherein one X is selected from the group consisting of a nucleoside, a nucleotide, an oligonucleotide, an activated nucleotide synthesis coupling moiety and a solid support linked to Y and the other X is selected from the group consisting of H PO 3   2- , a protecting group, a nucleoside, a nucleotide, and an oligonucleotide; and   wherein F is a functional group capable of linking an additional moiety or a functional group and said additional moiety linked thereto, wherein said additional moiety is selected from the group consisting of a reporter group, an oligonucleotide cleavage entity, an oligonucleotide binding agent, a membrane penetration enhancer, an oligonucleotide crosslinking agent and a protecting group.   
     
     
       2. The compound of claim 1 wherein one X is a protecting group and the other X is an activated nucleotide synthesis coupling moiety. 
     
     
       3. The compound of claim 1 wherein one X is a protecting group or H and the other X is a solid support linked to Y. 
     
     
       4. The compound of claim 1 wherein F is a protecting group linked to N. 
     
     
       5. The compound of claim 4 wherein n is 2-6. 
     
     
       6. The compound of claim 1 wherein F is -(CH 2 ) n'  Y'Pr wherein n' is 1-5, Y' is NH, O or S and Pr is a protecting group. 
     
     
       7. The compound of claim 1 wherein n is 2-6. 
     
     
       8. The compound of claim 7 wherein both Y are 0. 
     
     
       9. The compound of claim 1 wherein F is selected from the group consisting of ethyl, cholesteryl, acridine, anthraquinone, and rhodamine linked to N.